4′-Bromomethyl-2-cyanobiphenyl useful as a synthetic intermediate for pharmaceutical products, such as a compound having an anqiotensin II antagonistic action, is disclosed in EP0253310 and the like. Various production methods of 4′-bromomethyl-2-cyanobiphenyl have been heretofore reported.
JP-A-6-192170 describes a method for brominating 4-methylbiphenyl compound with a brominating agent, such as N-bromosuccinimide and the like, in a halogenated hydrocarbon solvent in the presence of an azobis-compound. However, this method uses expensive N-bromosuccinimide and the like as a brominating agent, and is industrially disadvantageous.
U.S. Pat. No. 5,621,134 (corresponding to EP0709369) describes a method for producing 4′-bromomethyl-2-cyanobiphenyl using economical bromine as a brominating agent in the presence of a radical initiator. However, this method uses an equimolar amount of bromine, thus by-producing hydrogen bromide. Because the by-produced hydrogen bromide inhibits bromination, further addition of a radical initiator is necessary to complete the reaction. Moreover, because bromine remaining in the reaction system colors the resulting product, further purification is necessary for industrial use.
JP-A-2002-88044 describes a method for removing by-produced hydrogen bromide from the reaction system, which comprises conducting the reaction described in the above-mentioned U.S. Pat. No. 5,621,134 (corresponding to EP0709369) under reduced pressure. However, this method requires special equipment for the reaction to be conducted under reduced pressure. In addition, equipment for treating hydrogen bromide gas, which is a strong acidic gas, is also necessary, and this method is not industrially advantageous. It is also an economically unbeneficial method, because one of the bromine atoms contained in bromine does not contribute to the reaction.
WO99/33788 describes a method comprising using, as a brominating agent, bromine produced by the reaction of aqueous hydrobromic acid with hydrogen peroxide and regenerating bromine by reacting hydrogen bromide, which is by-produced by bromination, with hydrogen peroxide. According to this method, however, 48% aqueous hydrobromic acid and 50% aqueous hydrogen peroxide need to be used, thereby increasing the amount of water in the reaction system, and volume efficiency becomes poor. In addition, highly concentrated aqueous hydrogen peroxide, which is dangerous in handling, needs to be used, and this method is not industrially advantageous.